Relationship between dietary patterns and diabetic microvascular complications in patients with type 2 diabetes mellitus.

OBJECTIVE: This study aimed to investigate the relationship between different dietary patterns and diabetic microvascular complications in patients with type 2 diabetes mellitus. PATIENTS AND METHODS: This study was conducted based on the Chinese Chronic Disease and its Risk Factor Surveillance System. A multi-stage stratified sampling method was used to randomly select two districts (Henghualing District, Taiyuan City, and Yuzi District, Jinzhong City) and two counties (Huguan County, Changzhi City, and Jiang County, Yuncheng City) from the chronic disease surveillance sites in Shanxi Province to collect general information, dietary records, physical measurements, and laboratory tests. In total, 1,227 patients were enrolled according to the study criteria. Factor analysis was performed to construct six dietary patterns, and the relationship between dietary pattern scores and type 2 diabetic microvascular complications was analysed using binary logistic regression after correcting for confounders. RESULTS: (1) Regarding the prevalence of type 2 diabetic microvascular complications and dietary characteristics, the prevalence of microvascular complications in patients with type 2 diabetes mellitus was 55.3% and was higher in urban than in rural areas. The prevalence of diabetic kidney disease (DKD), diabetic retinopathy, and diabetic peripheral neuropathy (DPN) were 21.4%, 12.7%, and 38.0%, respectively. (2) Six dietary patterns were constructed, namely, 'animal protein', 'coarse grains and plant protein', 'nuts and fruits', 'refined grains and vegetables', 'dairy', and 'added sugars', with factor contributions of 15.42%, 9.99%, 8.23%, 8.16%, 7.56%, and 7.28% respectively, explaining 56.64% of the total dietary variation. (3) After adjusting for confounding variables, the results of binary logistic regression indicated that patients in the highest quartile of dietary pattern scores for 'nuts and fruits' experienced a 43.3% lower risk of DKD compared to those in the lowest quartile [odds ratio (OR) = 0.567; 95% confidence interval (CI), 0.359-0.894; p < 0.001]. Similarly, patients in the highest quartile of dietary pattern scores for 'animal protein' had a 42.8% lower risk of DPN compared with those in the lowest quartile (OR = 0.572; 95% CI, 0.388-0.843; p < 0.05). CONCLUSIONS: The results of this study suggest that in patients with type 2 diabetes mellitus, a 'nuts and fruits' dietary pattern reduces the risk of DKD and an 'animal protein' dietary pattern reduces the risk of DPN.

Association between serum asprosin and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in the community.

OBJECTIVE: This study aimed to investigate the relationship between serum asprosin level and diabetic peripheral neuropathy (DPN) in community patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: A total of 498 patients with T2DM were recruited from Zhuoma Community Health Service Station and Chengbei West Street Community Health Service Center in Changzhi City of Shanxi Province between November 2019 and July 2021. Their height, weight, and body mass index (BMI), as well as fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), and serum asprosin levels, were analyzed. Patients were divided into the DPN group (n = 329) and the non-DPN group (n = 169) according to the presence or absence of DPN. The t-test, Mann-Whitney U test, and χ² test were used to compare the indicators between the two groups. Pearson or Spearman correlation analysis was used to evaluate the correlation between serum asprosin and other clinical data. Multivariate logistic regression analysis was used to analyze the influencing factors of DPN. RESULTS: Compared with the non-DPN group, the DPN group had higher serum asprosin (p < 0.05). The prevalence of DPN gradually increased according to the tertiles of asprosin (56%, 67%, and 75%; p < 0.05). Multivariate logistic regression analysis showed that after adjustment for covariates, patients with asprosin concentrations between 295.4-367.0 pg/ml and concentrations > 367.0 pg/ml had a higher risk of diabetic neuropathy compared than those with asprosin levels < 295.4 pg/ml (p < 0.05). CONCLUSIONS: Serum asprosin was found to be positively correlated with DPN, and it resulted as an influencing factor for DPN in patients with T2DM in the community. With the increase of asprosin, the risk of DPN also increased.

The effect of cytoplasmic dynein on the development and functional maintenance of retinal photoreceptor cells.

Cytoplasmic dynein is a multi-subunit complex that includes cytoplasmic dynein-1 (dynein1) and cytoplasmic dynein-2 (dynein2). It participates in various basic cellular processes, including nuclear migration, mitotic spindle organization, chromosome separation during mitosis, and the location and function of numerous intracellular organelles. Retinal photoreceptor cells are terminally differentiated neurons that cannot regenerate and cannot be replaced once lost. It is thus crucial to study their development to facilitate the generation and improvement of photoreceptor disease treatments. The outer segment (OS) of photoreceptor cells is a specific sensory cilium. An increasing number of studies have shown that cytoplasmic dynein plays an essential role in the development of retinal photoreceptor cells. To date, people have done a lot of studies on the various functions of dynein in cells and have a very detailed understanding. However, the role of dynein in retinal photoreceptor cells has not been summarized in detail. This article summarizes the currently available knowledge relating to the effects and mechanisms of cytoplasmic dynein on the development and functional maintenance of retinal photoreceptor cells.

MOTS-c improves osteoporosis by promoting the synthesis of type I collagen in osteoblasts via TGF-ß/SMAD signaling pathway.

OBJECTIVE: To investigate whether MOTS-c can regulate the synthesis of type I collagen in osteoblasts by regulating TGF-ß/SMAD pathway, thereby improving osteoporosis. MATERIALS AND METHODS: Viability of hFOB1.19 cells treated with MOTS-c was detected by CCK-8 assay. The mRNA and protein levels of TGF-ß, SMAD7, COL1A1 and COL1A2 in hFOB1.19 cells were detected by quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. We then changed expressions of TGF-ß and SMAD7 by plasmids transfection to detect levels of COL1A1 and COL1A2 in hFOB1.19 cells by qRT-PCR and Western blot, respectively. RESULTS: Cell viability was significantly increased after treatment of 1.0 µM MOTS-c for 24 h or 0.5 µM MOTS-c for 48 h in a time-dependent manner. The mRNA and protein expressions of TGF-ß, SMAD7, COL1A1 and COL1A2 in hFOB1.19 cells were dependent on the concentration of MOTS-c. In addition, MOTS-c increased the expressions of COL1A1 and COL1A2, which were partially reversed by knockdown of TGF-ß or SMAD7. CONCLUSIONS: MOTS-c could promote osteoblasts to synthesize type I collagen via TGF-ß/SMAD pathway.

Effects of constant and fluctuating temperature on the development of the oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae).

The oriental fruit moth, Grapholita molesta, is an important pest in many commercial orchards including apple, pear and peach orchards, and responsible for substantial economic losses every year. To help in attaining a comprehensive and thorough understanding of the ecological tolerances of G. molesta, we collected life history data of individuals reared on apples under different constant temperature regimes and compared the data with moths reared under a variable outdoor temperature environment. Because G. molesta individuals reared at a constant 25°C had the heaviest pupal weight, the highest survival rate from egg to adult, highest finite rate of increase, and greatest fecundity, 25°C was considered as the optimum developmental temperature. The G. molesta population reared at a constant 31°C had the shortest development time, lowest survival rate and fecundity, resulting in population parameters of r < 0, λ < 1, lead to negative population growth. The population parameters r and λ reared under fluctuating temperature were higher than that reared under constant temperatures, the mean generation time (T) was shorter than it was in all of the constant temperatures treatments. This would imply that the outdoor G. molesta population would have a higher population growth potential and faster growth rate than indoor populations raised at constant temperatures. G. molesta moths reared under fluctuating temperature also had a higher fertility than moths reared under constant temperatures (except at 25°C). Our findings indicated that the population raised under outdoor fluctuating temperature conditions had strong environment adaptiveness.

Aconitine induces cell apoptosis in human pancreatic cancer via NF-κB signaling pathway.

OBJECTIVE: Pancreatic cancer is one of the leading causes of death from cancer in European countries and the United States. This study sought to investigate the effects of aconitine, a well-known aconitum plant-produced toxin, on pancreatic cancer cell growth and apoptosis and to explore the potential mechanisms. MATERIALS AND METHODS: In this study, pancreatic cancer cell lines Miacapa-2 and PANC-1 were cultured, and cell viability was examined in these two cells treated with different doses of aconitine. Moreover, cell apoptosis was also analyzed upon aconitine treatment, and the specific mechanism was examined by Western blot assay and caspase activity detection. RESULTS: The results showed that aconitine inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. The administration of aconitine in Miapaca-2 and PANC-1 cells also induced cell apoptosis by upregulating the expression of pro-apoptotic factors Bax, cl-caspase-3, cl-caspase-9, and cleaved poly (ADP-ribose) polymerase 1 (PARP1), and by decreasing the anti-apoptotic Bcl-2 expression. More importantly, NF-κB was also decreased upon aconitine treatment. In a xenograft mouse model of pancreatic cancer, aconitine suppressed tumor growth and increased cell apoptosis. CONCLUSIONS: This study is the first report on the effects of aconitine on pancreatic cancer, and it reveals that aconitine may serve as a potent therapeutic strategy for clinical treatment of pancreatic cancer.

Heterologous expression of dammarenediol synthase gene in an engineered Saccharomyces cerevisiae.

AIMS: Dammarenediol production by an engineered yeast Saccharomyces cerevisiae was investigated. METHODS AND RESULTS: A dammarenediol-producing engineered yeast was constructed by heterologous expression of the dammarenediol synthase gene from Panax ginseng hairy roots through RT-PCR. Fermentation was carried out in a 5-L GRJY-bioreactor with an inoculum size of 1% v/v at 30°C. Dammarenediol detection was performed with silica gel chromatography and HPLC. Determination of dammarenediol synthase activity subcellular distribution was carried out by surveying the enzyme activity in microsomes, lipid particles and total yeast homogenate. When cultured under aerobic conditions, the engineered yeast could produce dammarenediol up to 250µgl(-1). However, when an anaerobic shift strategy was employed, dammarenediol accumulated at a level as twice as that under aerobic condition. The dammarenediol synthase and dammarenediol were mainly localized in lipid particles. CONCLUSIONS: Dammarenediol could be heterologously produced in engineered yeast. The heterologously expressed dammarenediol synthase is mainly localized in lipid particles. Anaerobic shift strategy could enhance the dammarenediol level in the engineered yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed that the high-value plant product dammarenediol could be produced by heterologous expression of the according gene in yeast. Furthermore, the anaerobic shift strategy could be potentially applied in oxidosqualene-derived compounds production in yeast. Here, the information about subcellular distribution of heterologously expressed dammarenediol synthase in the engineered yeast was also provided.

Hyperoxygenated solutions in clinical practice: preventing or reducing hypoxic injury.

In cases of hypoxia, oxygen can be supplied via a number of methods including face masks, nasal cannulae, hyperoxygenated oxygen chambers and mechanical ventilation. Administering oxygen via the respiratory tract is, however, limited in respiratory diseases such as pulmonary fibrosis, pneumoconiosis and severe acute respiratory syndrome, or following the inhalation of asphyxiating poisons. This has led to research into new methods of supplying oxygen that bypass the lungs. Research has investigated the efficacy of intravenous hyperoxygenated solutions (HOS) as auxiliary oxygen supplies in several hypoxic states including cardiopulmonary resuscitation, respiratory failure, cerebrovascular disease, myocardial ischaemia, severe acute respiratory syndrome, poisoning, neonatal hypoxia, altitude sickness, large burns and traumatic haemorrhagic shock. Much of the research has taken place in China and more than 3.5 million hypoxic patients have received HOS, with good therapeutic effects. This review summarizes the literature supporting the use of this novel treatment.

Emu model of full-range femoral head osteonecrosis induced focally by an alternating freezing and heating insult.

The emu, a large bipedal bird with hip joint biomechanics similar to humans, was used to establish an experimental model of femoral head osteonecrosis and subsequent femoral head collapse. Focal lesions were induced in 20 adult male emus using an alternating liquid nitrogen freezing and radiofrequency heating insult. At 2, 4, 8, 12 and 16 weeks post-surgery, hip magnetic resonance imaging (MRI) was performed. Before the emus were sacrificed, barium sulphate was infused to the lower extremity to study blood vessel distribution patterns. Femoral samples were scanned by micro-computed tomography (micro-CT) and evaluated histologically. Hip MRI showed changes from broad oedema to femoral head collapse. Emus developed a crippled gait from post-operative week 6. Micro-CT scans and histology showed human-like osteonecrotic changes with an impaired local blood supply. The protocol resulted in consistent full-range osteonecrosis of the femoral head that may serve as a model for testing potential treatments.

Activity of alpha2,6-sialyltransferase and its gene expression in peripheral B lymphocytes in patients with IgA nephropathy.

It is known that aberrant sialylation of IgA1 is involved in the pathogenesis of IgA nephropathy (IgAN). We hypothesize that aberrant sialylation of serum IgA1 may result from changes in the activity of alpha2,6-sialyltransferase (alpha2,6-ST) or expression of its coding gene ST6GALNAC2 in peripheral B lymphocytes. Sixty patients with IgAN and 20 healthy controls were enrolled. Peripheral B lymphocytes were isolated by CD-19-positive magnetic beads. The expression level of ST6GALNAC2 was quantitatively analysed by real-time reverse-transcriptase polymerase chain reaction (PCR). Serum IgA1 and sialylation levels were detected by enzyme-linked immunosorbent assay (ELISA) and specific lectin-binding ELISA. Activity of alpha2,6-ST was measured by specific lectin-binding ELISA. Expression of ST6GALNAC2 in B peripheral lymphocytes was significantly lower in patients with IgAN than that in normal controls (3.7 +/- 2.2 versus 6.3 +/- 2.3, P = 0.016); alpha2,6-ST activity in B lymphocytes was correlated positively with the level of alpha2,6-sialic acid in serum IgA1 in patients (n = 42) and controls (n = 12) (r = 0.37, P = 0.007). However, alpha2,6-ST activity did not differ between patients with IgAN and controls (1.19 +/- 1.43 versus 1.06 +/- 1.17, P > 0.05). These data suggested that reduced sialylation of serum IgA1 may result from decreased expression of ST6GALNAC2. The factors affecting activity of alpha2,6-ST in the sialylation of IgA1 need to be further investigated.

Differential binding characteristics of native monomeric and polymeric immunoglobulin A1 (IgA1) on human mesangial cells and the influence of in vitro deglycosylation of IgA1 molecules.

Recent studies had demonstrated that serum and mesangial immunoglobulin A1 (IgA1) in patients with IgA nephropathy (IgAN) were polymeric and deglycosylated. The current study was to investigate the binding characteristics of monomeric and polymeric normal human IgA1 on mesangial cells and the influence of in vitro deglycosylation of IgA1 molecules. The normal human IgA1 was desialylated and degalactosylated with specific enzymes, respectively. The monomeric IgA1 (mIgA1) and polymeric IgA1 (pIgA1) were separated by Sephacryl S-300 chromatography. The binding capacities of the mIgA1 and pIgA1 to primary human mesangial cells (HMC) were evaluated by classical radioligand assay. Both the native mIgA1 and pIgA1 could bind to HMC in a dose-dependent and saturable manner. The maximal binding capacity of the native pIgA1 were significantly higher than that of the native mIgA1 (P < 0.05). However, the affinity of the native mIgA1 was almost 100 times higher than that of the native pIgA1. After deglycosylation, binding of the two deglycosylated mIgA1 to HMC could not be detected. However, the maximal binding capacities of the two deglycosylated pIgA1 to HMC were increased significantly compared with that of native pIgA1. The affinity of the two deglycosylated pIgA1 was similar to that of native pIgA1 (P > 0.05). The current study suggests differential binding characteristics of native monomeric and polymeric IgA1 on mesangial cells. Glycosylation of IgA1 molecules could significantly affect the binding of IgA1 on HMC.

Self-aggregated deglycosylated IgA1 with or without IgG were associated with the development of IgA nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis, with various pathological phenotypes. Our previous study suggested that aberrant glycosylation of serum IgA1 was associated with different pathological phenotypes of IgAN, and substantial evidence indicated that deglycosylated IgA1 had an increased tendency to form macromolecules. The aim of the current study was to investigate the composition of IgA1-containing macromolecules in different pathological phenotypes of IgAN. Sera from 10 patients with mild mesangial proliferative IgAN (mIgAN), 10 with focal proliferative sclerosing IgAN (psIgAN) and 10 healthy blood donors were collected. The sera were applied and IgA1 binding proteins (IgA1-BP) were eluted from the columns immobilized with desialylated IgA1 (DesIgA1/Sepharose) or desialylated/degalactosylated IgA1 (DesDeGalIgA1/Sepharose), respectively. The amounts of IgA1 and IgG and the glycoform of IgA1 in the IgA1-BP were detected by enzyme-linked immunosorbent assays (ELISAs) and were compared between patients with different pathological phenotypes and normal controls. The amount of IgA1 in IgA1-BP eluted from both columns was significantly higher in patients with both pathological phenotypes of IgAN than in normal controls. In IgA1-BP eluted from DesDeGalIgA1/Sepharose, the desialylation of IgA1 was much more pronounced in patients with both pathological phenotypes of IgAN than in normal controls, while the degalactosylation of IgA1 was much more pronounced only in patients with psIgAN than in normal controls. Furthermore, the amount of IgG in IgA1-BP eluted from DesDeGalIgA1/Sepharose was significantly higher in patients with psIgAN than in normal controls. In patients with psIgAN, the amount of IgG eluted from DesDeGalIgA1/Sepharose was much greater than from DesIgA1/Sepharose. In conclusion, self-aggregated deglycosylated IgA1 with or without IgG were associated with the development of IgAN.

The glycans deficiencies of macromolecular IgA1 is a contributory factor of variable pathological phenotypes of IgA nephropathy.

Recent evidence has suggested that IgA1-containing macromolecules and the glycosylation of IgA1 in sera from patients with IgAN might involve the pathogenesis of IgAN. However, whether the different histological phenotypes can be attributed or not to the aberrant glycosylation of macromolecular IgA1 has not yet been elucidated. The aim of the current study is to investigate the glycosylation of IgA1 molecules in serum IgA1-containing macromolecules and their association with pathological phenotypes of IgAN. Sera was collected from 40 patients with IgAN and 20 donors. Twenty patients had mild mesangial proliferative IgAN, the remaining 20 had focal proliferative sclerosing IgAN. Polyethylene glycol 6000 was used to precipitate the macromolecules from sera of patients and controls. Biotinylated lectins were used in an enzyme-linked immunosorbent assay (ELISA) to examine different glycans on IgA1 molecules. The alpha2,6 sialic acid was detected by elderberry bark lectin (SNA) and the exposure of terminal galactose (Gal) and N-acetylgalactosamine (GalNAc) were detected by Arachis hypogaea (PNA) and Vilsa villosa lectin (VVL), respectively. The IgA1 glycans levels corrected by IgA1 concentrations were compared between patients and controls. Reduced terminal alpha2,6 sialic acid of IgA1 (79.89 +/- 25.17 versus 62.12 +/- 24.50, P = 0.034) was demonstrated only in precipitates from sera of patients with focal proliferative sclerosing IgAN, compared with those from controls. Reduced galactosylation of IgA1 molecules in precipitates was demonstrated in patients with both mild mesangial proliferative IgAN and focal proliferative sclerosing IgAN compared with normal controls (24.52 +/- 18.71 versus 76.84 +/- 32.59 P = 0.000 and 33.48 +/- 25.36 versus 76.84 +/- 32.59 P = 0.000). However, no significant difference was found in IgA1 glycosylation in the supernatant between patients and normal controls (P > 0.05). The glycosylation deficiency of IgA1 existed only in serum IgA1-containing macromolecules of patients with IgAN, and was associated with the renal pathological phenotypes. This suggests that aberrant glycosylation of IgA1 in serum macromolecules might be a contributory factor in the pathogenesis of IgAN.